The overall focus of the Center for Child Environmental Health Risk Research is on mechanisms that define children's susceptibility to pesticides. The Molecular Mechanisms Study will specifically evaluate the molecular and cellular mechanisms of toxicity through which pesticides can exert their neurodevelopmental toxicity. Alterations in the regulatory dynamics of neural cell proliferation, differentiation, and cell death will be examined. The functional consequences of these will be assessed in the Neurobehavioral Assessment Facility Core. These studies will complement the Genetic Susceptibility Research Projects where the impacts of genetic variability in organophosphate pesticide metabolism will be examined. In total these three laboratory based studies provide an optimal mix of in vivo and in vitro assessments and molecular, cellular, and genetic evaluations. These laboratory findings will fit directly into the Risk Characterization Core and its biologically based dose response models. Information from the Exposure Assessment Facility Core will ensure that these quantitative assessments are realistic.